Weiliang Kong

Introduction: Paraquat (PQ) poisoning causes high mortality via acute lung injury (ALI) driven by excessive reactive oxygen species (ROS) in pulmonary microvascular endothelial cells. We developed BR@Lipo-CerTP, a lung-targeted nanotherapeutic using C16-ceramide-binding peptide-modified bilirubin liposomes, to enhance endothelial delivery and treat PQ-induced ALI. Methods: BR@Lipo-CerTP was characterized for physicochemical properties and cellular uptake in pulmonary microvascular endothelial cells (PMVECs). In vitro efficacy was assessed via cytotoxicity, apoptosis, ROS, antioxidant capacity, and mitochondrial function assays in PQ-exposed PMVECs. Multi-omics analysis elucidated therapeutic mechanisms. In vivo efficacy and biosafety were evaluated in a PQ-induced ALI mouse model through survival, histopathology, edema, and toxicity assessments. Results: BR@Lipo-CerTP exhibited uniform ~120 nm spherical morphology, narrow size distribution, excellent stability, and enhanced PMVEC uptake versus non-targeted liposomes. In vitro, it significantly attenuated PQ-induced cytotoxicity, apoptosis, and ROS accumulation while restoring antioxidant capacity and mitochondrial function. Multi-omics revealed it disrupts a vicious cycle of glutathione depletion, ferroptosis, and NF-κB/NLRP3-driven inflammation, resetting pathological crosstalk between redox homeostasis, regulated cell death, and immune activation. In vivo, BR@Lipo-CerTP markedly improved survival, alleviated pulmonary damage and edema, suppressed oxidative stress and inflammation, with no systemic toxicity. Discussion: Pulmonary endothelial-targeted bilirubin delivery effectively mitigates PQ-induced ALI by coordinately regulating redox balance, cell death, and inflammation. This strategy offers a promising nanotherapeutic for PQ poisoning and other ROS-driven pulmonary diseases, highlighting targeted nanomedicine’s potential in toxicological emergencies.

We explored the relationship between the oxidative balance score (OBS) and all-cause, as well as cause-specific mortality, within a large and nationally representative sample. A total of 30,074 adults participated in this prospective study, utilizing data from the National Health and Nutrition Examination Survey cycles spanning 1999 to 2018 in the United States. Mortality outcomes were determined through linkage to National Death Index records up to December 31, 2019. OBS was computed based on 16 dietary and 4 lifestyle components. Cox proportional hazards models and restricted cubic splines were employed to estimate associations between OBS and mortality across all-cause, cancer, cardiovascular disease (CVD), and respiratory disease. Over the mean 10.3 years of follow-up, we observed 3561 deaths. In comparison to the lowest OBS quartile, individuals in the highest quartile exhibited a significantly reduced multi-adjusted hazard ratio of 0.66 (95% confidence interval [CI]: 0.56–0.78), 0.56 (95% CI: 0.40–0.77), and 0.43 (95% CI: 0.22–0.83) for all-cause, cancer, and respiratory disease mortality, respectively. However, no significant association was found for CVD mortality (0.80 [95% CI: 0.59–1.09]). Restricted cubic splines demonstrated a linear association. Sensitivity analysis and subgroup analysis confirmed the stability of results for all-cause and cancer mortality, while respiratory disease mortality might be influenced by chronic disease. A robust negative correlation was identified between OBS and all-cause, cancer, and respiratory disease mortality, with no such association observed for CVD mortality. This study provides insights into enhancing overall antioxidant dietary and lifestyle practices among adults.

Stress hyperglycemia ratio (SHR), an index reflecting relative hyperglycemia under stress conditions, has been linked to adverse outcomes in various clinical settings. However, its prognostic significance in individuals with nonalcoholic fatty liver disease (NAFLD) remains poorly understood. This study aimed to examine the association between SHR and mortality risk in adults with NAFLD. We analyzed 12,604 adults with NAFLD from the NHANES 1999–2018 database. Multivariable Cox proportional hazards models, restricted cubic spline (RCS) analysis, and Fine–Gray competing risk models were employed to evaluate associations between SHR and all-cause and cardiovascular mortality, During an overall mean follow-up time of 99.26 months, a U-shaped relationship was observed between SHR and all-cause mortality in adults aged 40–59 years and ≥ 60 years. Risk increased at both low and high SHR levels, with identified thresholds at 0.89 for middle-aged and 0.94 for older adults. No significant association was found with cardiovascular mortality. Findings were consistent across subgroups. SHR showed a U-shaped association with all-cause mortality in middle-aged and older adults with NAFLD. Monitoring SHR may help identify high-risk individuals and guide clinical management.

Low muscle mass is a critical indicator of frailty and adverse health outcomes. However, the potential link between systemic oxidative stress and low muscle mass remains underexplored. This study aims to investigate the association between the Oxidative Balance Score (OBS) and low muscle mass in U.S. adults. In this cross-sectional study, data from 4096 adults aged 20 to 59 years from National Health and Nutritional Examination Survey (NHANES) 2011 to 2018 were analyzed. Low muscle mass, the primary outcome, was evaluated utilizing the Foundation for the National Institutes of Health (FNIH) definition. Analysis involved the application of restricted cubic splines and weighted multivariate regression techniques. A nonlinear association was observed between OBS and low muscle mass (p for nonlinearity < 0.0049). Compared to the lowest OBS quartile, individuals in the highest quartile had an adjusted OR of 0.26 (95% CI: 0.14–0.48) for low muscle mass (P for trend < 0.001). Additionally, the adjusted β value for ALM/BMI was 0.067 (95% CI: 0.053–0.082), P for trend < 0.001. Both dietary and lifestyle OBS also showed negative associations with low muscle mass, with fully adjusted ORs of 0.38 (95% CI: 0.19–0.76) and 0.17 (95% CI: 0.05–0.62), respectively (both P for trends < 0.01). Furthermore, in stratified analyses, this relationship was particularly prominent in the 40–59 years age group (P for interaction = 0.048). Higher OBS, indicative of greater antioxidant exposure, was robustly associated with a lower risk of low muscle mass, particularly in 40–59 old adults. These findings underscore the potential role of oxidative balance in preserving muscle health and highlight the need for targeted interventions in this demographic. Further longitudinal studies are warranted to confirm these associations and evaluate potential clinical applications.

Background: Exposure to brominated flame retardants (BFRs) has been linked to age-related diseases. This study investigates the associations between both individual and combined BFRs exposures and phenotypic age acceleration (PhenoAgeAccel) in U.S. adults.Methods: Data from 3,908 U.S. adults from NHANES 2005–2010 were analyzed. Generalized linear regression models (GLMs) assessed the associations between individual BFRs and PhenoAgeAccel, while weighted quantile sum (WQS) regression and Bayesian Kernel Machine Regression (BKMR) analyses were used to evaluate the effects of combined BFRs exposures.Results: GLMs indicated significant positive associations between several BFRs and PhenoAgeAccel, including PBDE28 (β = 0.55, 95% CI: 0.13, 0.96), PBDE85 (β = 0.42, 95% CI: 0.11, 0.74), PBDE47 (β = 0.39, 95% CI: 0.04, 0.75), PBDE99 (β = 0.38, 95% CI: 0.07, 0.68), and PBDE154 (β = 0.37, 95% CI: 0.04, 0.70). RCS analysis confirmed nonlinear dose–response relationships for PBDE47 and PBDE99 (P for nonlinearity = 0.03361 and 0.0233, respectively). Stratified analyses revealed that males were more susceptible to BFRs exposure effects, particularly for PBDE99 (P for interaction = 0.027) and PBDE209 (P for interaction = 0.005). The WQS regression showed a significant association between combined BFRs exposure and increased PhenoAgeAccel (β = 0.504, 95% CI: 0.071, 0.937), with PBB153 and PBDE153 as key contributors. BKMR analysis indicated a trend of increasing PhenoAgeAccel with higher BFR exposure levels, primarily driven by PBDE99.Conclusion: This study highlights the significant positive associations between individual and combined BFR exposures and PhenoAgeAccel, with males potentially being more vulnerable to these effects.

Background: The rising intake of ultra-processed foods (UPFs) has been linked to adverse health outcomes, yet its impact on aging acceleration remains unclear.Objective: This study aimed to examine the association between the percentage of total daily calories (%Kcal) and grams (%Gram) from UPFs and phenotypic age acceleration (PhenoAgeAccel).Methods: Data from 12,079 adults in the NHANES 2005–2010 cycles were analyzed. The relationship between UPFs intake and PhenoAgeAccel was assessed using multivariable linear regression and restricted cubic splines, with adjustments for relevant covariates. The mediating role of body mass index (BMI) was also explored.Results: A significant positive linear association was observed between UPFs intake (%Gram) and PhenoAgeAccel, with the highest quartile showing an increase of 0.60 (95% CI: 0.15, 1.05; p for trend = 0.039), but no association was found between UPFs intake (%Kcal) and PhenoAgeAccel. Mediation analysis indicated that BMI mediated 27.5% of the association between UPFs intake (%Gram) and PhenoAgeAccel. Sensitivity analyses confirmed the robustness of the results.Conclusion: Higher intake of UPFs intake (%Gram) is positively associated with PhenoAgeAccel, with BMI playing a significant mediating role.

Background: Few studies have investigated the associations between perchlorate, nitrate, and thiocyanate (PNT) and biological aging. This study aimed to assess the association between PNT and biological aging among U.S. adults.Methods: Utilizing multivariable linear regression and restricted cubic splines (RCS), we analyzed urinary PNT levels’ impact on phenotypic age and biological age. Subgroup and sensitivity analyses were also conducted. Weighted Quantile Sum (WQS) and Bayesian Kernel Machine Regression (BKMR) models examined PNT mixtures.Results: 8,368 participants were analyzed. Mean phenotypic age was 43.05 ± 0.48 years, mean biological age was 47.08 ± 0.4 years. Multivariable linear regression showed significant negative associations between higher PNT levels and phenotypic age (perchlorate β = −0.6, 95% CI: −0.93 to −0.27; nitrate β = −0.81, 95% CI: −1.19 to −0.42; thiocyanate β = −0.56, 95% CI: −0.77 to −0.34) after covariates adjusted. RCS demonstrated negative nonlinear relationships between PNT exposure and phenotypic age (nonlinear p values: 0.002, β = −0.78, 95% CI: −1.13 to −0.44), indicating a consistent negative linear relationship observed through RCS and remaining stable across sensitivity analyses. WQS regression revealed a negative association between the mixture and phenotypic age in both positive and negative directions, with a significant negative association with biological age in the negative direction. BKMR analysis revealed a negative association between PNT mixtures and phenotypic age, with nitrate and thiocyanate identified as the primary predictors of phenotypic age. No association found between PNT mixture and biological age.Conclusion: Individual or combined PNT are negatively associated with phenotypic age. High nitrate is associated with reduced biological age, showcasing consistent outcomes.

Background: Food insecurity (FI) has been a global threat, as a social determinant in connection with the prevalence of diseases requiring dietary interventions, such as asthma, has been established. This study aims to examine the relationship between FI and respiratory health outcomes.Methods: This cross‐sectional study included 7626 children and 17 530 adults from the 2007 to 2012 National Health and Nutritional Examination Surveys (NHANES) in the United States. Weighted multivariate regression models were used to evaluate the associations between FI and respiratory outcomes, including current asthma, wheezing, fractional exhaled nitric oxide (FeNO), and lung function.Results: The weighted prevalence of high FI was 19.68% in children and 13.74% in adults. In adults, high FI was significantly associated with current asthma (OR: 1.41, 95% CI: 1.19–1.67) and wheezing (OR: 1.72, 95% CI: 1.48–1.99). The association with asthma was stronger in women (p for interaction = 0.02) and non‐Hispanic Whites (p for interaction = 0.04), whereas wheezing showed stronger associations in non‐Hispanic Whites (p for interaction = 0.01). High FI was linked to lower percent‐predicted forced expiratory volume in 1 s (FEV₁) in children (β: −15.93%, 95% CI: −27.82%, −4.03%) and adults (β: −1.13%, 95% CI: −2.22%, −0.04%) without asthma or wheezing. Additionally, high FI was inversely associated with FeNO in adults with current asthma (β: −3.36, 95% CI: −5.54, −1.17) and wheezing (β: −4.40, 95% CI: −7.79, −1.02).Conclusions: FI is associated with increased asthma and wheezing in adults, particularly among women and non‐Hispanic Whites, and with reduced FEV1 in both adults and children without asthma and wheezing.

Background: Preserved Ratio Impaired Spirometry (PRISm) is increasingly recognized as a precursor to Chronic Obstructive Pulmonary Disease (COPD). The impact of Ultra-Processed Foods (UPFs) intake on PRISm and lung function remains underexplored, and we aimed to explore their associations.Methods: This study included 8,336 U.S. adults. Weighted logistic and linear regression models were employed for main analysis. Dose–response relationship was examined through restricted cubic spline (RCS) analysis, and subgroup analyses explored interactions with selected covariates.Results: Participants in the PRISm group were older and exhibited various adverse health characteristics. The percentage of total daily energy intake from UPFs (%Kcal) intake was associated with a non-significant increase in PRISm risk (OR 1.67, 95% CI: 0.96–2.92, p = 0.07). However, the highest quartile of UPFs (%Kcal) intake was significantly linked to increased PRISm risk (OR 1.36, 95% CI: 0.99–1.86, P for trend = 0.043). Furthermore, higher UPFs (%Kcal) intake negatively affected lung function, with participants in the highest quartile showing a significant reduction in forced expiratory volume in 1 s (FEV1) of −45.5 mL (95% CI: −87.6 to −3.4, P for trend = 0.045) and a decrease in forced vital capacity (FVC) of −139.4 mL (95% CI: −223.5 to −55.4, p < 0.001) compared to those in the lowest quartile. RCS analysis demonstrated linear relationships for both PRISm and lung function. Subgroup analysis revealed increased susceptibility primarily among individuals with occupational exposure. Additionally, sensitivity analysis indicated that a higher percentage of total daily intake from UPFs (%Grams) intake was significantly associated with an increased risk of PRISm (OR 1.86, 95% CI: 1.07–3.25, p = 0.03).Conclusion: Higher intake of UPFs is linked to an increased risk of PRISm and negatively affects lung function, particularly in individuals with occupational exposure.

Background: Previous studies have demonstrated a significant association between serum vitamin A concentration and non-alcoholic fatty liver disease (NAFLD) development. However, the long-term prognostic implications of serum vitamin A in patients with NAFLD remain underexplored. This study aims to investigate whether there exists a correlation between serum vitamin A concentrations and overall mortality among subjects diagnosed with NAFLD.Methods: To investigate the association between serum vitamin A concentrations and NAFLD outcomes, we conducted prospective cohort studies using data from the 1999–2006 and 2017–2018 National Health and Nutrition Examination Survey (NHANES). We utilized a multivariate Cox regression model to explore the relationship between serum vitamin A levels and all-cause mortality. Survival curves related to serum vitamin A were constructed using the Kaplan–Meier method. Additionally, the restricted cubic splines (RCS) method was applied to examine potential nonlinear relationships between serum vitamin A concentrations and all-cause mortality of NAFLD.Results: Over a median follow-up period of 10.3 years, a total of 1,399 all-cause deaths were recorded. The weighted average concentration of serum vitamin A was 61.48 ± 0.37 μg/dL. After adjusting for potential confounders, a significant U-shaped relationship was identified between serum vitamin A concentrations and the risk of all-cause mortality in NAFLD patients. This relationship was particularly pronounced in men and elderly individuals aged 60 to 85.Conclusion: Our study reveals a significant non-linear relationship between serum vitamin A concentrations and the risk of all-cause mortality in patients with NAFLD. These findings underscore the importance of monitoring and maintaining optimal serum vitamin A levels to potentially improve survival outcomes in NAFLD patients.